DESCRIPTION: (Applicant's Description) This project studies the potential improvements allowed in clinical treatment planning through the use of a more sophisticated and generalized automated plan optimization process. The overall goal of this project is to demonstrate and then evaluate the improvements and changes which result from improved sophistication of the automated optimization process, with the intended aim of enhancing the physician's ability to make improved, more quantitative decisions trading off normal tissue dose, tumor dose, complexity, and many other issues. This project will determine whether this enhanced optimization capability will allow the physician to create optimized plans which will achieve the desired clinical goals and be reliably delivered with assurance that the patient's actual resulting dose distributions will closely match the design. The project will demonstrate and evaluate the potential benefits of plan optimization which 1) accounts for a number of clinical realities such as geometrical uncertainties and treatment delivery time limitations, 2) makes use of more sophisticated cost functions, 3) utilizes multistep or multilayer optimization strategies, and 4) incorporates all available enhancements to investigate the utility of dynamic refinement, which involves re-optimization of the patient's treatment plan(s) taking into account issues which arise throughout the time of the patient's treatment course. This project will utilize developments and information obtained by the other projects, including delivery and dosimetric constraints and issues from Project 2, patient setup and organ motion uncertainties issues and algorithms from Project 3, and clinical protocols, data, plans, and plan evaluations involved in the clinical protocols and treatments performed by Project 4. The capabilities and evaluations obtained through the course of this work will also be available for the optimization-related studies in Projects 2 and 3, and will be used in the development of improved clinical treatment plans and treatment planning and optimization protocols for use in the Project 4 clinical studies. The improvements developed, studied and evaluated by this project should lead to much more clinically relevant plan optimization, making possible improved and more successful patient treatments.